Csl Limited · ASX:CSL
Csl — Investor Day (December 2015)
127 slides from Csl's investor day presentation, Dec 10, 2015
Slide 1: Investor R&D Briefing
For personal use only Investor R&D Briefing December 10, 2015 1
Slide 2: Global Legal Notice
Global Legal Notice For personal use only Forward looking statements The materials in this presentation speak only as of the date of these materials, and include forward looking statements about CSL Limited and its related bodies corporate (CSL) financial results and estimates, business prospects an
Slide 3: Global Agenda
Global Agenda For personal use only • Welcome Mark Dehring • Introduction & Highlights Andrew Cuthbertson • Research & Early Development Andrew Nash • Immunoglobulins & Specialty Products • Clinical Development Charmaine Gittleson • Commercial Opportunities Bob Repella • Q&A Break • Coagulation/Haem
Slide 4: Introduction and Highlights
For personal use only Introduction and Highlights 4
Slide 5: CSL Protein Therapeutics Technical Platform
Global CSL Protein Therapeutics Technical Platform For personal use only Breakthrough Medicines Immunoglobulins Specialty Products Haemophilia Products Plasma Recombinant Fractionation Technology Protein Science 5
Slide 6: CSL R&D Strategy
Global CSL R&D Strategy For personal use only Breakthrough • Maintain commitment Medicines to extracting maximum value from existing assets and supporting and improving current products Immunoglobulins Specialty Products • Develop new protein-based therapies for treating serious illnesses focusing o
Slide 7: Commitment to Research & Development
Global Commitment to Research & Development For personal use only R&D Investment* (US$ millions) New Product Development activities focus on innovative new therapies for life- threatening diseases. Market Development strategies seek to bring therapies to new markets and new indications. Life Cycle D
Slide 8: Leveraging Global Capabilities
Global Leveraging Global Capabilities For personal use only >1,100 scientists globally 8
Slide 9: R&D Portfolio – December 2014
Global R&D Portfolio – December 2014 For personal use only Research Pre-clinical Phase I Phase II Phase III Registration Commercial/ Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH Immunoglobulins Haemophilia Life Cycle Specialty Management# Products Influenza Vaccine Hizentra® CIDP Hizentr
Slide 10: Progress through Stage Gates in 2015
Global Progress through Stage Gates in 2015 For personal use only Privigen Hizentra ® US Japan Flex Dosing CSL640 CSL627 Voncento ® rIX-FP subct rVIII-SC US VWD EU CSL650 CSL627 rVWF-FP rVIII-SC EU CSL312 Respreeza® Anti-FXIIa EU CSL324 GCSFR Quad Flu Vaccine 18+ p.ging/POD CSL362* OH-CRC Janssen 10
Slide 11: R&D Portfolio – December 2015
Global R&D Portfolio – December 2015 For personal use only Research Pre-clinical Phase I Phase II Phase III Registration Commercial/ Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH Immunoglobulins Haemophilia Life Cycle Specialty Management# Products Influenza Vaccine Hizentra® CIDP C1-inh
Slide 12: Research & Early Development
For personal use only Research & Early Development 12
Slide 13: CSL's Global Research Capability
Global CSL’s Global Research Capability For personal use only • Coordinated global project portfolio Specialty Breakthrough Immunoglobulins Haemophilia Products Medicines • Hub (Bio21, Parkville) & spoke model • Research excellence in therapeutic proteins • Plasma and recombinant manufacturing platf
Slide 14: Haemophilia Research Strategy
Haemophilia Research Strategy For personal use only • Major focus on patient QoL Novel Strategies – Coag Factor • Extract maximum value and performance from existing assets Maximising Value and Performance Addressing • Develop new protein-based Inhibitors therapies and strategies for treating of Exi
Slide 15: Haemophilia Research – Half life extension
Haemophilia Research – Half life extension For personal use only • Improved prophylaxis for haemophilia patients Product Features Phase Manufacturer Half-life extension Eloctate rFVIII fused to Fc Market Biogen Idec N8-GP BDD FVIII O-linked pegyln Ph II/III Novo Nordisk BAX 855 FVIII Lys-linked pegy
Slide 16: Haemophilia Research – FVIII half life extension
Haemophilia Research – FVIII half life extension For personal use only • VWF – Albumin fusion protein (VWF-FP) • Haemophilia A patients have normal levels of VWF FP VWF FVIII After 9 hrs the majority of FVIII is associated with endogenous VWF FP VWF FVIII VWF VWF FVIII T1/2 3-4 days T1/2 16 hrs • Cr
Slide 17: Haemophilia Research – FVIII half life extension
Haemophilia Research – FVIII half life extension For personal use only modVWF-FP PK • modVWF-FP PK study in NHPs x modVWF-FP (ng/ml) x D 'D 3 [ n g /m l] x x x x x CSL627 Haemate® P pd VWF + CSL627 modVWF-FP dose 1 + CSL627 modVWF-FP dose 2 + CSL627 modVWF-FP dose 3 + CSL627 • Prolongation of FVIII
Slide 18: Haemophilia Research – Subcutaneous Delivery
Haemophilia Research – Subcutaneous Delivery For personal use only Enabling more flexible and convenient prophylaxis in haemophilia patients • New, innovative and unique administration form • Patients with poor venous access • Reduction or avoidance of indwelling catheters & associated complications
Slide 19: Haemophilia Research – Subcutaneous Delivery
Haemophilia Research – Subcutaneous Delivery For personal use only • Subcutaneous delivery of rIX-FP (haemophilia B mice) 250 100 rIX-FP 125 IU/kg s.c rIX-FP 250 IU/kg s.c FIX activity (% norm) 200 80 rIX-FP 125 IU/kg i.v BeneFIX 250IU/kg s.c 150 rIX-FP 125 IU/kg s.c 60 100 40 50 20 0 0 0 20 40 60 8
Slide 20: Haemophilia Research – Subcutaneous Delivery
Haemophilia Research – Subcutaneous Delivery For personal use only • rIX-FP s.c efficacy in haemophilia B mice Total blood loss Bleeding time 400 2500 * Vehicle * CSL654 250IU/kg 2000 300 * n.s. BeneFIX 250IU/kg * * Seconds 1500 µL 200 1000 100 500 0 0 • rIX-FP reduces total blood loss and bleeding
Slide 21: Breakthrough Medicines
Breakthrough Medicines For personal use only • Leveraging clinical and technical Breakthrough insight in developing novel protein- Medicines based therapies o Significant unmet need Specialty o Multiple indications Immunoglobulins Products • Key Focus Haemophilia o CSL362 (Janssen) Products o CSL324
Slide 22: CSL362 – Acute Myeloid Leukaemia
Breakthrough Medicines CSL362 – Acute Myeloid Leukaemia For personal use only • Most common acute leukaemia in adults • Incidence increases with age • Untreated AML fatal: 3 – 4 months • Chemotherapy → 50-75% CR ~70% will relapse • CSL362 MOA – targets CD123 overexpressed on leukaemic cells o engine
Slide 23: CSL362 – Acute Myeloid Leukaemia (Janssen licence)
Breakthrough Medicines CSL362 – Acute Myeloid Leukaemia For personal use only • Licence Agreement with Janssen Biotech – June 2013 o CSL responsible for completing CSL362 AML Phase 1 clinical study Milestone Date Phase 1 Last Patient Last Visit July 2015 o Janssen responsible for all further oncolog
Slide 24: CSL362 – Acute Myeloid Leukaemia
Breakthrough Medicines CSL362 – Acute Myeloid Leukaemia For personal use only • CSL362 depletes biomarker pDC’s and basophils in patients 24
Slide 25: CSL362 – AML Conclusions
Breakthrough Medicines CSL362 – Acute Myeloid Leukaemia For personal use only Conclusions • Manageable safety profile: • Pre-medication with steroids required to prevent infusion reactions • PD effects confirming CD123-targeted ADCC • Rapid and full depletion of basophils and pDCs o Sustained deplet
Slide 26: CSL362 – SLE
Breakthrough Medicines CSL362 – SLE For personal use only • pDCs contribute to a disease amplification loop in SLE CSL362 Janssen to commence exploratory study in SLE patients 2H 2016 26
Slide 27: CSL324 – Chronic and Acute Inflammation
Breakthrough Medicines CSL324 – Chronic and Acute Inflammation For personal use only CSL324 – anti-G-CSFR mAb • Targeting the G-CSF receptor represents a novel approach to the treatment of neutrophil mediated pathologies • Efficacy in multiple animal models of inflammatory disease COPD exacerbations
Slide 28: CSL324 – Early clinical development strategy
Breakthrough Medicines CSL324 – Chronic and Acute Inflammation For personal use only • Early clinical development strategy Safe, well tolerated Determine dose & interval Phase Ib Proof of Phase I FIH (SAD) Principle in Patients Study (Neutrophilic Dermatoses) • GLP toxicology completed, CSL324 safe
Slide 29: CSL Research Summary
Global CSL Research Summary For personal use only • Portfolio of early stage opportunities consistent with CSL commercial objectives Specialty Breakthrough Immunoglobulins Haemophilia Products Medicines • Delivery of high quality candidates for clinical development o CSL362 (anti-IL-3R, partnered wi
Slide 30: Immunoglobulins
30 For personal use only Immunoglobulins
Slide 31: Immunoglobulins
Immunoglobulins For personal use only • Maintaining leadership position Breakthrough through focus on: Medicines o New Indications o Geographic expansion Specialty o Delivery options Immunoglobulins Products • Key Focus Haemophilia o Hizentra® Products o Privigen® 31
Slide 32: Immunoglobulins: Privigen and Hizentra
Immunoglobulins For personal use only Privigen® Hizentra® • The first and only 10% liquid • The first 20% high concentration low intravenous immunoglobulin (IVIG) volume SCIG for convenient self therapy that is proline stabilized administration providing steady-state with room temperature storage up
Slide 33: Immunoglobulins Progress in Neurology
Immunoglobulins Progress in Neurology For personal use only Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) • Build on Privigen® experience in CIDP • Introduce SC infusion method o Ease of administration o Steady state levels, manages wear off effect 33
Slide 34: Immunoglobulins PATH Program
Immunoglobulins PATH Program For personal use only • Pivotal study o Largest randomised placebo controlled study in CIDP (16 countries/69 sites) o Study screening completed (n=289) o 71 patients have completed the primary study o Last patient completing Q4 2016 • FDA and EMA submissions 2H 2017 • PM
Slide 35: Subcutaneous Infusions Made Simple
Immunoglobulins Subcutaneous Infusions Made Simple For personal use only • 83% (n=100) patients said medication in its current form was easy to use (120 subject responses at week 9) 35
Slide 36: Subcutaneous Infusions Can Be Individualised
Immunoglobulins Subcutaneous Infusions Can Be Individualised For personal use only • Clinical trial highest dose/volume required – 160mL in avg 80kg patient o 4 infusions sites/session/~120 minute infusion time o 2 infusion sites/session x 2 days ~60 minute infusion time • Infusion volume of 50mL/si
Slide 37: Portfolio Expansion in Japan
Immunoglobulins Portfolio Expansion in Japan For personal use only • ~3,500 Primary Immunodeficiency patients in Japan PID network (2014) • Currently Hizentra® and 5% IVIG available to patients • CSL will bring first high purity room temperature 10% IVIG product to Japan • Commence Privigen® PID stu
Slide 38: Commercial Opportunities and Activities
For personal use only Commercial Opportunities and Activities 38
Slide 39: Global Plasma-proteins Therapeutics Market
Global Plasma-proteins Therapeutics Market For personal use only Immunoglobulin $8.0B Haemophilia $10.5B Total Global Market Value: ~$25.0B Specialty $2.9B Albumin $3.3B Sources: Company annual reports/financial schedules, MRB global Coagulation Factors Concentrate Market 2014 & 2015, MRB WW Plasma
Slide 40: CSL Plasma-proteins Therapeutics Portfolio
Global CSL Plasma-proteins Therapeutics Portfolio For personal use only CSL FY15 Sales $5.0B $2,326M Immunoglobulin Immunoglobulin $1,026M Haemophilia Haemophilia Albumin $923M Specialty Specialty $754M Albumin 40
Slide 41: Immunoglobulins Global Market
Immunoglobulins Global Market For personal use only Hyper $1.0B SCIG $0.6B • IVIG continues to hold largest share of market Total Global Market Value: • Increasing acceptance and growth ~$8.0B of SCIG IVIG $6.4B Sources: Company annual reports, Markets and Markets Plasma Fractionation Report 2015, b
Slide 42: Immunoglobulins CSL's Global Performance
Immunoglobulins CSL’s Global Performance For personal use only CSL FY15 Sales $2.326B Key Brands: IVIG SCIG Hyper 42
Slide 43: Immunoglobulins Continued Market Growth
Immunoglobulins Continued Market Growth For personal use only US-PPTA Data (Kg, 000) Per-Capita IG Use 70 USA Canada Australia 65 Sweden 8.5% CAGR France 60 Spain Italy UK 55 Germany Japan South Korea 50 Hong Kong Singapore China 45 Poland Chile Malaysia 40 Argentina Brazil Taiwan 35 Russia Thailand
Slide 44: Immunoglobulin Today, Tomorrow, Future
Immunoglobulin Today, Tomorrow, Future For personal use only Today Tomorrow Future • Privigen® CIDP • Hizentra® CIDP • Approval of new growth in Europe and development program indications Canada • Continued global • Pursue new • Hizentra® launches therapeutic areas individualized therapy • Evaluatin
Slide 45: Specialty Products
45 For personal use only Specialty Products
Slide 46: Specialty
Specialty For personal use only • Leveraging high quality broad product portfolio through: Breakthrough Medicines o New markets o Novel indications Immunoglobulins o Novel modes of administration Specialty Products • Key Focus o Beriplex®/Kcentra® Haemophilia Products o Berinert®, CSL830 o Zemaira®/
Slide 47: Kcentra / Beriplex
Specialty Kcentra® / Beriplex® For personal use only • Prothrombin Complex Concentrate = PCC (4FPCC) o Vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) • Indicated as an agent to reverse the effects of vitamin K antagonists (e.g. Warfarin) for: o Bleeding related to over-anticoagulation
Slide 48: Beriplex Expansion in Japan
Specialty Beriplex® Expansion in Japan For personal use only • Clinical study evaluating vitamin K antagonist reversal in acute bleeding and for surgery o Open label study almost completed o Demonstrated effective INR reversal at 30 minutes o No safety concerns o PMDA submission Q2 2016 • Availabili
Slide 49: Potential New Usage for 4FPCC
Specialty Potential New Usage for 4FPCC For personal use only Coagulation Cascade and Mechanisms of Anti-coagulation FII FVII FIX FX 49
Slide 50: Reversal of Anti-coagulation Effect in a Bleeding Patient
Specialty For personal use only Reversal of Anti-coagulation Effect in a Bleeding Patient • Antidotes being developed to reverse the anti-coagulation activity of Factor Xa or IIa inhibitors o Studies demonstrate normalisation of clotting tests o Bleeding studies not yet available • 4FPCCs in healthy
Slide 51: 4FPCC in the Control of Bleeding – Animal Data
Specialty For personal use only 4FPCC in the Control of Bleeding – Animal Data Data represent medial plus interquartile range. Shaded area represents sham treated control range. References: Pragst et al. JTH 2012; 10(9): 1841-48. Herzog et al. Thromb Res 2014; 134(3):729-36. Dickneite and Hoffman 20
Slide 52: Kcentra / Beriplex in Treatment of Acute Major Bleeding
Specialty For personal use only Kcentra® / Beriplex® in Treatment of Acute Major Bleeding Related to FIIa or FXa Inhibitor Use • USA and international expert groups recommend inclusion of PCC in guidelines as agent to reverse anticoagulant effect of NOACs1,2,3 • Hospital treatment algorithms increas
Slide 53: Hereditary Angioedema (HAE): Berinert and CSL830
Specialty Hereditary Angioedema (HAE) For personal use only Berinert® CSL830 • Plasma derived, pasteurised and • Plasma derived, pasteurised and nanofiltered concentrate of C1 nanofiltered higher concentrated C1 Esterase Inhibitor indicated for the Esterase Inhibitor indicated for the intravenous tr
Slide 54: Complement Pathway and HAE
Specialty Complement Pathway and HAE For personal use only -ve -ve -ve 54
Slide 55: Clinical Presentation
Specialty Clinical Presentation For personal use only 55
Slide 56: The Impact of HAE on Patients
Specialty The Impact of HAE on Patients For personal use only • HAE is unpredictable • All body sites are associated with impairment; not just laryngeal attacks • It impacts people not just during attacks, but also in between attacks • Attacks are associated with significant anxiety: this anxiety is
Slide 57: HAE attack frequency does not link with severity
Specialty For personal use only HAE attack frequency does not link with severity 1-24 25-52 53-104 >104 attacks/year attacks/year attacks/year attacks/year ~78% ~13% ~6% ~3% Still has significant disease burden 57
Slide 58: Subcutaneous Dosing Maintains Trough above Protective C1-INH Level
Specialty For personal use only Subcutaneous Dosing Maintains Trough above Protective C1-INH Level 100 C1-INH functional activity (%) SC low 40IU/kg IU/kg SC high IU/kg 1000 IU IV 1000 60 IU/kg IU/kg 80 60 • SC trough remains above predictive 40% threshold 40 40% activity • Potential for reduced 20
Slide 59: CSL830 Program Progress
Specialty CSL830 Program Progress For personal use only • Phase III study rapidly completed enrollment (n=90) • Patients moving into extension study o Allowed for individualised dosing o Well tolerated o No withdrawals for lack of efficacy • Submission to FDA and EU anticipated 2H 2016 59
Slide 60: Bringing new technologies to the HAE space
Specialty For personal use only Bringing new technologies to the HAE space CSL312 – Anti XIIa monoclonal antibody FXIIa MAb 60
Slide 61: CSL312 Development Plan – HAE Therapy
Specialty CSL312 Development Plan – HAE Therapy For personal use only • New molecule and target – potential benefit: o In refractive patients o For HAE types I, II and III as well as ACE inhibitor induced oedema o For subcutaneous delivery every 2 to 4 weeks o Other indications • Commence first in m
Slide 62: Respreeza / Zemaira
Specialty Respreeza® / Zemaira® For personal use only • Respreeza® is a highly purified alpha-1 therapy approved by EMA for maintenance treatment to slow the progression of emphysema in adults with severe alpha-1 antitrypsin deficiency (AATD) • RAPID trial is largest placebo controlled study in pati
Slide 63: Alpha-1 Antitrypsin Deficiency (AATD)
Specialty Alpha-1 Antitrypsin Deficiency (AATD)1 For personal use only Normal Alpha-1 antritrypsin deficiency (AATD) AAT coats the lungs, Lungs lack AAT coating and protecting them from NE are open to attack from NE Blood vessel Blood vessel Liver Liver AAT is released from the liver into the AAT ac
Slide 64: AATD Leads to Lung Tissue Deterioration
Specialty For personal use only AATD Leads to Lung Tissue Deterioration Images from high-resolution computerised tomography scanning A B normal lung (left; A) severe emphysema (right; B) References: http://www.ctsnet.org/portals/thoracic/newtechnology/article-4 64
Slide 65: RAPID Program – Respreeza Slowed Rate of Lung Density Decline
Specialty For personal use only RAPID Program – Respreeza® Slowed Rate of Lung Density Decline from Baseline Annualised rate of decline in physiologically adjusted PI15 lung density (g/L) at TLC over 48 months* (ITT population)1,2 A1- Placebo 0 PI • Difference in annual decline from Annual rate of d
Slide 66: Estimate of Long-Term Clinical Benefit
Specialty For personal use only Estimate of Long-Term Clinical Benefit1,2 Extrapolation of Respreeza® effect on the predicted time to reach terminal respiratory function (data from the RAPID trial)1,2 • RAPID program Projected survival difference demonstrates a 60 specific treatment A1- No treatment
Slide 67: Commercial Opportunities and Activities
For personal use only Commercial Opportunities and Activities 67
Slide 68: Specialty Global Market
Specialty Global Market For personal use only Other ~$0.3B Acquired Bleed • Orphan/rare diseases ~$0.6B • Unmet medical need Total Global Market Value: • Often under or misdiagnosed ~$2.9B HAE ~$1.2B • Awareness and education AATD ~$0.8B • Significant patient value Sources: Company annual reports/fi
Slide 69: Specialty CSL's Global Performance
Specialty CSL’s Global Performance For personal use only • Increase demand • Geographical expansion • Appropriate diagnosis CSL FY15 Sales $923M Key Brands: Acquired Bleeding Other HAE AATD 69
Slide 70: Specialty Acquired Bleeding (Beriplex/Kcentra)
Specialty Acquired Bleeding (Beriplex®/Kcentra®) For personal use only Warfarin Reversal NOAC Reversal • Indicated for patients with acute • Evaluating clinical development major bleeds, requiring urgent options surgery or invasive procedure • Potential benefit in patients with • Data published in L
Slide 71: Specialty Hereditary Angioedema (HAE)
Specialty Hereditary Angioedema (HAE) For personal use only Berinert® CSL830 CSL312 • C1-INH for acute • C1-INH for prophylaxis • Fully human, high treatment affinity mAb targeting • Phase III pivotal study FXIIa • Fast relief of pain and fully enrolled swelling • Activation of FXIIa is • Subcutaneo
Slide 72: Specialty AATD (Hereditary Emphysema)
Specialty AATD (Hereditary Emphysema) For personal use only Zemaira® Respreeza® • Indicated in the US for chronic • Approved in the EU for hereditary augmentation and emphysema 3Q2015 maintenance therapy • EU API market is ~$200M USD • Ongoing education programs to support appropriate diagnosis • De
Slide 73: Q&A
73 For personal use only Q&A
Slide 74: Break
74 For personal use only Break
Slide 75: Investor R&D Briefing
For personal use only Investor R&D Briefing December 10, 2015 75
Slide 76: Haemophilia Products
For personal use only Haemophilia Products 76
Slide 77: Haemophilia
Haemophilia For personal use only • Supporting and enhancing plasma Breakthrough products and developing novel Medicines recombinant portfolio with focus on: o Scientific and product innovation o Patient benefit Immunoglobulins Specialty Products • Key Focus Haemophilia o IDELVIONTM (rIX-FP) Product
Slide 78: PROLONG-9FP Clinical Development Program IDELVION
Haemophilia For personal use only PROLONG-9FP Clinical Development Program IDELVIONTM (rIX-FP) References: www.clinicaltrials.gov 78
Slide 79: rFIX Albumin Fusion Protein
Haemophilia rFIX Albumin Fusion Protein For personal use only Activation cleavage sites Factor IX Albumin ASPPP AP Linker ..NWIKEKTKLTPVSQTSKLTRAETVFPDVDAHKSEVAHR.. • rIX-FP is o A recombinant protein purified from CHO cells o Generated by the genetic fusion of recombinant albumin to rFIX PROLONG-9F
Slide 80: PROLONG-9FP Clinical Trial Program
Haemophilia PROLONG-9FP Clinical Trial Program For personal use only Phase I Phase I/II Phase II/III Phase III Phase IIIb (extension) • PK • PK • PK • In children • 21 day prophylaxis • Safety • Long-term safety • Long-term safety • PK • Surgical arm • Weekly prophylaxis • 7-, 10-, and 14-day • 7-da
Slide 81: Adult Study Flow Chart (Study 3001)
Haemophilia Adult Study Flow Chart (Study 3001) For personal use only Period: Screening PK Treatment EOS Up to 14 days 30 days On-Demand Group 2 On-demand 7-day prophylaxis Subject rIX-FP Flow: PK 14-day prophylaxis Prophylaxis 7-day prophylaxis 10-day prophylaxis Group 1 7-day prophylaxis PK assess
Slide 82: IDELVION shows sustained activity above 5% out to 14 days
Haemophilia For personal use only IDELVIONTM shows sustained activity above 5% activity out to 14 days 80 70 Previous FIX 12-65y (n=12) FIX Activity (IU/dL, %) rIX-FP 50IU/kg 12-65y (n=46) 60 50 40 Day 7 30 13.8 Day 10 9.6 20 Day 14 6.1 10 5% activity level 0 0 24 48 72 96 120 144 168 192 216 240 26
Slide 83: rIX-FP prophylaxis reduced spontaneous and overall bleeding rate
Haemophilia For personal use only rIX-FP prophylaxis reduced spontaneous and overall bleeding rate Within-subject comparison (n=19) rIX-FP Adult On-Demand vs. AsBR Prophylaxis On-demand Prophylaxis reduction period period ~6 months ~12 months 15.43 0.0 100% AsBR, median (IQR) (7.98–17.96) (0.00–0.96
Slide 84: rIX-FP Effective in 7 and 14 day regimens in Adults
Haemophilia For personal use only rIX-FP Effective in 7 and 14 days regimens in Adults Within-subject comparison 7-day 14-day n=21 n=21 0.0 0.0 AsBR, median (IQR) (0.0, 0.0) (0.0, 1.0) Median dose (IU/kg) 40 IU/kg 75 IU/kg AsBR – annualised spontaneous bleeding rate; IQR – interquartile range 84
Slide 85: Paediatric Reduction of ABR among previously on-demand patients
Haemophilia For personal use only Paediatric Reduction of ABR among previously on-demand patients AsBR Total ABR Weekly rIX- Subject Age FP dose Prior to study In study Prior to study In study (IU/kg) 1 8y 31 3.5 39 5.9 65 IU/kg 2 7y 34 2.4 42 4.7 65 IU/kg 3 4y 15 0 19 1.2 50 IU/kg ABR – annualised
Slide 86: Low Bleeding Rates During Weekly Prophylaxis in Children
Haemophilia For personal use only Low Bleeding Rates During Weekly Prophylaxis Treatment in Children Age 6-11 Age <6 years ABR years (n=12) (n=15) Median 0.00 0.78 Spontaneous IQR 0.00, 0.10 0.00, 1.99 Median 0.5 1.13 Total Joint IQR 0.00, 1.45 0.00, 2.36 1 Median 2.61 3.4 Total IQR 2.00, 6.48 0.76,
Slide 87: Patients respond to long-term prophylaxis therapy
Haemophilia For personal use only Patients respond to long-term prophylaxis therapy (4.2 years) in PROLONG-9FP program 30 Spontaneous ABR Mean Annualized Bleeding Rate 25 Total ABR 20 15 10 5 0 ODT 7-day PT 14-day PT Reduction in ABR and AsBR in patients moving from on-demand to long term prophylaxi
Slide 88: PROLONG-9FP Program
Haemophilia PROLONG-9FP Program For personal use only • Extension study ongoing EMA post marketing commitment o Previously untreated patients being enrolled • Adult and pediatric indications under review by EMA and FDA • FDA and Canadian approval expected Q1 2016 • EMA approval expected Q2 2016 88
Slide 89: rVIII-SingleChain (CSL627)
Haemophilia rVIII-SingleChain (CSL627) For personal use only Me++ A1 A2 A3 C1 C2 rVIII-SingleChain 89
Slide 90: AFFINITY Clinical Trial Program
Haemophilia AFFINITY Clinical Trial Program For personal use only Phase I/III Study 1001 - COMPLETED Phase III Study 3002 Extension Study 3001 • PK • Pediatric • Adult • Long-term safety COMPLETED • Pediatric • On-demand treatment • PUPs • Long-term prophylaxis • Surgical prophylaxis Study 3001 Ongo
Slide 91: AFFINITY Study demonstrated
Haemophilia AFFINITY Study demonstrated For personal use only • Improved PK: o Lower clearance, greater AUC and longer half-life compared with otcocog alfa • Well tolerated locally and systemically • Excellent efficacy controlling bleeds and for surgical procedures 91
Slide 92: rVIII-SingleChain effective in 2x and 3x weekly Prophylaxis
Haemophilia For personal use only rVIII-SingleChain effective in 2x and 3x weekly Prophylaxis Regimen • On demand arm (n=27) o median ABR = 19.64 • Prophylaxis arm (n=146) o median ABR = 1.14 o median AsBR = 0.00 • Comparable ABR in the 2x and 3x week regimens ABR – annualised bleeding rate; AsBR –
Slide 93: rVIII reported Median ABR
Haemophilia rVIII reported* Median ABR For personal use only Individualized 3x Weekly 2x Weekly Weekly (mean 3.5 days) ABR AsBR ABR AsBr ABR AsBr ABR AsBr 1.14 rVIIISC 1.14 0 0 (20-50IU/kg) Efmorotocog alfa1 1.6 3.6 (rVIII Fc fusion) (25-65IU/kg) (65IU/kg) BAX8552 1.9 0 (rVIII pegylated) (40-50IU/kg
Slide 94: rVIII-SingleChain AFFINITY Program
Haemophilia rVIII-SingleChain AFFINITY Program For personal use only • Extension study ongoing fulfilling EMA post marketing commitment o Previously untreated patients being enrolled • Accepted by FDA June 2015, approval expected mid 2016 • Filed to EMA December 2015 94
Slide 95: rVIIa-FP (CSL689)
Haemophilia rVIIa-FP (CSL689) For personal use only rFVIIa Linker rAlbumin 95
Slide 96: Congenital Haemophilia with Inhibitors (CHwI)
Haemophilia Congenital Haemophilia with Inhibitors (CHwI) For personal use only • Occurs when patient develops inhibitory antibodies to the coagulation factor (FVIII or FIX) • Genetic predisposition / mutations • Occurs early, highest risk in previously untreated patients o 34% inhibitor incidence,
Slide 97: Role of rVIIa-FP in CHwI
Haemophilia Role of rVIIa-FP in CHwI For personal use only • rVIIa-FP can lead to the formation of a stable hemostatic plug to control bleeding o works locally by binding to tissue factor exposed at the site of vascular injury o Also binds to factor X on activated platelets 97
Slide 98: CSL689 has longer half life than rFVIIa
Haemophilia CSL689 has longer half life than rFVIIa For personal use only • CSL689 half-life = 8.5 hrs1 o Potential to dose 2-3 x weekly o Possibility of on demand and manageable prophylaxis regimen • rFVIIa (Novoseven) half life ~2-3hrs o Indicated for treatment of bleeding episodes- requires dosin
Slide 99: rVIIa-FP Clinical Development Program
Haemophilia rVIIa-FP Clinical Development Program For personal use only Congenital Haemophilia with Inhibitors Phase I (Healthy Volunteers) Phase II/III PK PK Phase III Long-term safety Safety On-demand Prophylaxis Surgery COMPLETED ONGOING • Pivotal Phase II/III trial in haemophilia A & B patients
Slide 100: PROLONG-7FP Clinical Development Program
Haemophilia PROLONG-7FP Clinical Development Program For personal use only Congenital Factor VII Deficiency Phase I (Patients) Phase II/III PK Prophylaxis Safety On-demand EXTENSION ONGOING PLANNING • Phase I PK/PD study in congenital FVII deficiency patients o PK and safety in patients o Commenced
Slide 101: Commercial Opportunities and Activities
For personal use only Commercial Opportunities and Activities 10 1
Slide 102: Haemophilia Global Market
Haemophilia Global Market For personal use only VWD $0.5B Hem B • Trend toward recombinants in $1.3B developed markets Total Global • New longer-acting product Inhibitor Market Value: launches Bleed Therapy ~$10.5B Hem A $2.2B $6.5B • 75% of patients with bleeding disorders are under/un-treated Sour
Slide 103: Haemophilia CSL's Global Performance
Haemophilia CSL’s Global Performance For personal use only Grow range of differentiated pd and recombinant therapies • Broad portfolio presence • Growth in developed and emerging markets • Continued balance between recombinant and plasma derived portfolio CSL FY15 Sales $1,026M Key Brands: Recombina
Slide 104: Haemophilia Key Growth Drivers
Haemophilia Key Growth Drivers For personal use only Breakthrough Medicines • Successfully launch the new recombinant products globally Immunoglobulins Specialty • Position IdelvionTM (rIX-FP) as the Products new SOC for haemophilia B Haemophilia • AfstylaTM (rVIII-SingleChain) Products product prof
Slide 105: Idelvion (rIX-FP)
Haemophilia IdelvionTM (rIX-FP) For personal use only • Unique recombinant albumin fusion protein molecule • Pharmacokinetic profile includes extended half-life and greater area under the curve (AUC) resulting in increased activity levels Attributes of Albumin Potential Differentiated Profile • Natu
Slide 106: Afstyla (rVIII-SingleChain)
Haemophilia AfstylaTM (rVIII-SingleChain) For personal use only • Single chain design with most of B-domain deleted • Covalent link between heavy and light chains Single Chain Design Potential Differentiated Profile • Strong affinity to vWF • Twice-weekly dosing • Greater molecular integrity and • E
Slide 107: rVIIa-FP
Haemophilia rVIIa-FP For personal use only • Prophylaxis and treatment of adult, adolescent and pediatric patients with congenital haemophilia A or B with inhibitors and congenital FVIIa deficiency Attributes of rVIIa-FP Potential Differentiated Profile • Unique recombinant albumin fusion • Fast, ef
Slide 108: Haemophilia Today, Tomorrow, Future
Haemophilia Today, Tomorrow, Future For personal use only Today Tomorrow Future • Helixate® • IdelvionTM • rVIIa–FP • Beriate® • AfstylaTM • Subcutaneous rIX-FP • Humate® • True long-acting rVIII • Mononine® 10 8
Slide 109: Breakthrough Medicines
For personal use only Breakthrough Medicines 10 9
Slide 110: Breakthrough Medicines
Breakthrough Medicines For personal use only • Leveraging clinical and technical insight in developing novel protein- based therapies Breakthrough Medicines o Significant unmet need o Multiple indications Specialty Immunoglobulins Products • Key Focus o CSL112 (Apo AI) Haemophilia o CSL324 (anti-G-C
Slide 111: Breakthrough Medicines Acute Coronary Syndrome (ACS)
Breakthrough Medicines Acute Coronary Syndrome (ACS) For personal use only 11 1
Slide 112: A High Unmet Medical Need in ACS
Breakthrough Medicines For personal use only Reduction of Early Recurrent Cardiovascular Events – A High Unmet Medical Need in ACS • Recurrent CV events occur early, are associated with high mortality and are inadequately addressed by available therapies References: Figure adapted from PLATO Trial,
Slide 113: Cardioprotective Role of High Density Lipoprotein
Breakthrough Medicines For personal use only Cardioprotective Role of High Density Lipoprotein • HDL exerts cardio protective effect through cholesterol efflux o movement of excess cholesterol from arterial-wall macrophages o leads to reduction in plaque size and risk of rupture Cholesterol Efflux C
Slide 114: CSL112 raises ABCA1 Cholesterol Efflux Capacity
Breakthrough Medicines For personal use only CSL112 raises ABCA1 Cholesterol Efflux Capacity • Impaired cholesterol efflux, inflammation and plaque rupture, all exist in the setting of ACS o Contribute to the high incidence of early recurrent cardiovascular events • CSL112 results in a profound, imm
Slide 115: CSL112 – A Novel Therapy for Acute Coronary Syndrome
Breakthrough Medicines For personal use only CSL112 – A Novel Therapy for Acute Coronary Syndrome Cholesterol removal from atherosclerotic plaque CSL112 infusion Liver uptake Biliary excretion Atherosclerotic plaque lesion CSL112 has the potential to rapidly reduce the high rate of early recurrent C
Slide 116: CSL112 Phase 2B
Breakthrough Medicines CSL112 Phase 2B For personal use only Proof of mechanism and demonstration of safety Randomisation N = 1200 Four Weekly Infusions High dose (6 gms) Low Dose (2 gms) Placebo N = 400 N = 400 N = 400 • 1,258 patient post myocardial infarction trial fully recruited • Data Monitori
Slide 117: CSL112 Clinical Program
x Breakthrough Medicines xClinical Program For personal use only Phase 2b Dose-ranging / POC Moderate RI safety (Ph2) • ACS population • Higher risk ACS population • Safety, efflux biomarker, pop PK • Safety, pop PK • Normal and mild RI • Start up stage • Enrollment completed LPLV Q2 2016 Phase 3 Pi
Slide 118: Influenza Vaccines R&D
For personal use only Influenza Vaccines R&D 11 8
Slide 119: Vaccines Core Flu Products
Vaccines Core Flu Products For personal use only • Differentiated, adjuvanted influenza vaccine for 65yr+ and young children • Elderly indication approved in >30 countries (US approval Nov 2015) • Paediatric indication in Canada • World’s first cell-culture flu vaccine • Currently registered for 18y
Slide 120: Vaccines Key R&D Programs
Vaccines Key R&D Programs For personal use only TIV Filed • Expanding age indication to 4yr+ Cell culture QIV Filed • Filed for US approval Anticipate launch in 2016 Adjuvanted QIV Phase III • Filing in 2016 QIV Filed • Age ≥ 18 yrs Anticipate soft launch in 2016 QIV Phase III • Age ≥ 5yrs, filing 2
Slide 121: Summary
1 12 For personal use only Summary
Slide 122: R&D Portfolio – December 2015
Global R&D Portfolio – December 2015 For personal use only Research Pre-clinical Phase I Phase II Phase III Registration Commercial/ Phase IV CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH Immunoglobulins Haemophilia Life Cycle Specialty Management# Products Influenza Vaccine Hizentra® CIDP C1-inh
Slide 123: Expected Progress in next Months
Global Expected Progress in next 12 Months For personal use only Privigen Nebulised Ig Japan CSL640 rIX-FP rIX-FP rIX-FP subct Japan US Approval Mod VWF rVIII-SC rIX-FP LA rVIII Japan EU Approval Haptoglobin/ rVIII-SC Hemopexin US Approval CSL312 CSL830 rVIII-SC Anti-FXIIa C1-INH s.c. EU Approval CS
Slide 124: Significant Target Launch Dates
Global Significant Target Launch Dates For personal use only 2015 2016 2017 2018 2019 2020 Voncento™ CSL654 CSL654 CSL689 rVIIa-FP V WD EU rIX-FP US rIX-FP Japan Inhibitors CSL654 CSL627 rVIII -SC rIX-FP EU EU/Japan CSL627 rVIII-SC US Respreeza® CSL830 C1-INH EU SubCut Beriplex® Japan Hizentra® CIDP
Slide 125: 2015 Highlights
Global 2015 Highlights For personal use only • Hizentra® flexible dosing registration in US Immunoglobulins • Hizentra® CIDP pivotal study recruitment completed • Respreeza® registration in Europe Specialty Products • Berinert® s.c. pivotal Phase III recruitment completed • rIX-FP effective in 7-14
Slide 126: Q&A R&D Briefing
6 12 For personal use only Q&A R&D Briefing
Slide 127: Further Information
Global Further Information For personal use only Presentation Playback A playback of the Research and Development presentations will be available for a period of two weeks following R&D Briefing. Investors wishing to listen to these presentations should contact CSL Investor Relations to arrange acce